Efficacy of Artesunate-amodiaquine and Artemether-lumefantrine for Treatment of Plasmodium Falciparum Malaria in Liberia

Malaria Clinical Trial

Official title:

Efficacy of Artesunate-amodiaquine (ASAQ) and Artemether-lumefantrine (AL) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Liberia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06300970
• Other study ID #: 0900f3eb81e634a9
• Status: Completed
• Phase: Phase 4
• Start date: August 9, 2022
• Est. completion date: August 16, 2023

Study information

• Verified date: May 2024
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the efficacy of both first-line antimalarial medications used for the treatment of uncomplicated Plasmodium falciparum malaria infections in two geographic regions in Liberia.

Description:

Title: Efficacy of artesunate+amodiaquine (ASAQ) and artemether+lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in Liberia

Objective: To assess the efficacy of both first-line ASAQ and AL for the treatment of uncomplicated P. falciparum malaria infections

Study Sites: Sacleapea Comprehensive Health Center, Saclepea-Mah District in Nimba County; and Sinje Health Center, Garwula District, Sinje, in Grand Cape Mount County

Study Period: August 2022 to August 2023

Study Design: Prospective study of two cohorts with simultaneous enrolment of each therapy

Patient population: Patients aged 6 to 59 months with confirmed uncomplicated P. falciparum infection

Sample Size: Total number of patients to be enrolled is 352 patients. This consists of 88 patients per arm per site. There are two arms in each of the two sites.

Treatment(s) and follow-up: Patients enrolled in the ASAQ arm will receive the treatment once daily dose for three days. Patients enrolled in the AL arm will receive treatment twice daily dose for three days. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy.

Primary endpoints: The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.

Secondary endpoints: The frequency and nature of adverse events will be recorded.

Exploratory endpoints: Any polymorphisms of molecular markers for antimalarial drug resistance and prevalence of HRP2 deletions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 352
• Est. completion date: August 16, 2023
• Est. primary completion date: August 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 59 Months

Eligibility

Inclusion Criteria

1. Age between 6 to 59 months (5 years)

2. Weight = 5 kg

3. Monoinfection with P. falciparum with a parasite density of 2,000 to 200,000 asexual forms per microliter of blood

4. Axillary temperature =37.5°C or history of fever in the last 24 hours

5. Hemoglobin = 8.0g/dl

6. Easy access to the health facility and ability to return to the health facility over the course of the four weeks of follow-up

7. Informed consent of parent or guardian

Exclusion Criteria on Day 0

1. Any danger signs or signs of severe malaria (see Appendix I)

2. Pneumonia or bronchopneumonia

3. Severe malnutrition (Z-score < 3)

4. History of taking antimalarials (or antibiotics with antimalarial activity such as cotrimoxazole, tetracycline or doxycycline) in the last 14 days

5. Mixed malaria infection

6. History of hypersensitivity or allergy to the medication

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Plasmodium Falciparum
• Uncomplicated Malaria

Intervention

Drug:
• Amodiaquine-artesunate (ASAQ)
Oral medication given for treatment of uncomplicated plasmodium falciparum infection.
• Artemether+Lumefantrine (AL)
Oral medication given for treatment of uncomplicated plasmodium falciparum infection.

Locations

Country	Name	City	State
Liberia	Saclepea-Mahn Comprehensive Health Center Saclepea-Mahn District, Nimba County	Saclepea	Nimba County
Liberia	Sinje Health Center, Garwula District, Sinje, Grand Cape Mount County	Sinje	Grand Cape Mount County

Sponsors (2)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Ministry of Health, Liberia

Country where clinical trial is conducted

Liberia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of samples with confirmed Histidine-rich protein 2/3 (HRP2/3) gene deletions	Molecular data on hrp2/hrp3 deletions will be tabulated and frequencies will be calculated from samples collected during the study, approximately 4 weeks.	Samples collected from participants during the study, approximately 4 weeks.
Other	Number of samples with molecular markers of anti-malarial resistance	Molecular data on drug resistance polymorphisms will be tabulated and frequencies will be calculated from samples collected during the study, approximately 4 weeks.	Samples collected from participants during the study, approximately 4 weeks.
Primary	Number of Participants with Early Treatment Failure (ETF)	Danger signs or severe malaria on day 1, 2, or 3 in the presence of parasitemia; A parasitemia on day 2 higher than day 0; Axillary temperature = 37.5 °C on day 3 in the presence of parasitemia; Parasitemia on day 3 = 25% of day 0 parasitemia	Day 1 to day 3 following treatment.
Primary	Number of Participants with Late Treatment Failure (LTF)	Danger signs, signs of severe malaria, or axillary temperature > 37.5 °C in the presence of parasitemia on any day between day 4 and day 28 in patients who did not previously meet any of the criteria of early treatment failure; Presence of parasitemia (with a parasite with the same genotype as day 0) on any day between day 7 and day 28 regardless of temperature in patients who did not previously meet any of the criteria of early treatment failure	Day 4 to day 28 following treatment.
Primary	Number of Participants with Adequate Clinical and Parasitological Response (APCR)	• Absence of parasitemia on day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure, reinfection or late parasitological failure.	Day 28 following treatment.
Secondary	Number of Patients with Adverse Events	An adverse event is defined as any unfavorable, unintended sign, symptom, syndrome or disease that develops or worsens with the use of a medicinal product, regardless of whether it is related to the medicinal product during participation in the study, approximately 4 weeks.	During participation in the study, approximately 4 weeks.